Varenicline Ameliorates Learning and Memory Deficits in Amyloid β(25–35) Rat Model of Alzheimer’s Disease

Introduction: Alzheimer’s disease (AD) is a enfeeble neurodegenerative disorder characterized by increased β-amyloid (Aβ) deposition and neuronal dysfunction leading to impaired learning and recall. Among proposed risk factors, impaired cholinergic transmission is a main cause for incidence of disease. Methods: In the present study, effects of the intracerebroventricularly administration of an agonist of nicotinic cholinergic receptors, varenicline(0.5 and 2 μg/μl), on learning and memory impairments induced by intrahippocampal Aβ(25–35) injection was assessed in rats. Results: The results showed that the intrahippocampal Aβ(25–35) injected rats exhibit lower spontaneous alternation score inY-maze tasks (p<0.05), impaired retention and recall capability in the passive avoidance test (p<0.05), and fewer correct choices (p<0.001) and more errors(p<0.001) in the RAM task. Varenicline, almost in both doses, significantly improved alternation score in Y-maze task (p<0.001), impaired retention and recall capability in the passive avoidance test (p<0.05), and correct choices in the RAM task (p<0.001). Discussion: This study indicates that varenicline pretreatment attenuates Aβ- induced impairment of short-term spatial memory in rats probably due to its agonist activity at nicotinic receptors.